Nab-paclitaxel and Gemcitabine Hydrochloride Followed by Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

NCT02427841 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB00011256NCI-2015-00498SOL-14124-L
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well nab-paclitaxel and gemcitabine hydrochloride followed by radiation therapy before surgery work in treating patients with pancreatic cancer that can be removed by surgery. Chemotherapy drugs, such as nab-paclitaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving nab-paclitaxel, gemcitabine hydrochloride, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• R0 Resection Rate Defined as Macroscopically Complete Tumor Removal With Negative Microscopic Surgical Margins by Pathologic Assessment

  The R0 resection rate, measured as the percent of participants achieving R0 resection among those who initiate study drug, will be computed with 95% confidence interval. A 2-sided binomial test will be used to determine whether the R0 resection rate is significantly greater than 0.37 at 10% significance level.

  At the time of surgery

Secondary Outcomes (5)

• Incidence of Toxicity According to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 4.0

  From the first dose of study drug(s) until 28 days after last study intervention, up to approximately 3 years, 10 months

• Overall Survival Rate Defined as the Percentage of Subjects Alive at the 2 Year Time Point

  From first dose of study drug until 2 years or time of death by any cause, which ever comes first. Participants are assessed every 3 months after completing study interventions.

• Overall Survival Rate Defined as the Percentage of Subjects Alive at the One Year Time Point

  From first dose of study drug until 1 year or time of death by any cause, whichever comes first. Participants are assessed every 3 months after completing study interventions.

• Relapse-free Survival Rate Defined as the Percentage of Subjects Who Are Without Recurrence or Death at One Year From Surgical Resection of the Primary Tumor

  From time of resection until progression or death by any cause, within 1 year of resection. Participants are assessed by imaging every 3 months after completing study interventions.

• Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Defined as the Percent of Subjects With Complete or Partial Disease Response as Confirmed Through Tumor Imaging With Computed Tomography (CT)

  From first dose of study drug(s), with assessments at Staging 1 (approximately 2 months) and Staging 2 (approximately 5 months after first dose of study drug(s)).

Study Arms (1)

Treatment (chemotherapy, chemoradiation therapy, surgery)

EXPERIMENTAL

PRE-OPERATIVE (NEOADJUVANT) CHEMOTHERAPY: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo IG-IMRT 5 days a week for 28 fractions and receive fluorouracil IV continuously on days 1-7 for 6 weeks. SURGICAL RESECTION: Patients undergo surgery 4-10 weeks after the last dose of chemoradiation. POST-OPERATIVE (ADUJUVANT) CHEMOTHERAPY: Beginning within 8-12 weeks after surgery, patients receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4 additional courses in the absence of disease progression or unacceptable toxicity.

Drug: Fluorouracil; Drug: Gemcitabine; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Nab-paclitaxel; Procedure: Therapeutic Conventional Surgery

Interventions

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (chemotherapy, chemoradiation therapy, surgery)

Gemcitabine DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine, Gemzar, LY-188011, LY188011

Treatment (chemotherapy, chemoradiation therapy, surgery)

Image Guided Radiation Therapy RADIATION

Undergo IG-IMRT

Also known as: IGRT, image-guided radiation therapy

Treatment (chemotherapy, chemoradiation therapy, surgery)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IG-IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (chemotherapy, chemoradiation therapy, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, chemoradiation therapy, surgery)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, nanoparticle paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel

Treatment (chemotherapy, chemoradiation therapy, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (chemotherapy, chemoradiation therapy, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed adenocarcinoma of the pancreas
• Tumors must be localized (non-metastatic) and classified as borderline resectable according to Americas Hepato-Pancreato-Biliary Association (AHPBA)/Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT) consensus criteria or be clinically node-positive via computed tomography (CT) or endoscopic ultrasound
• AHPBA/SSO/SSAT criteria (any one of the following):
• Tumor-associated deformity of the SMV (superior mesenteric vein) or PV (portal vein)
• Abutment of the SMV or PV \>= 180 degrees
• Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction
• Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction
• Abutment of the superior mesenteric artery (SMA) \< 180 degrees
• Subjects must have measurable disease (by RECIST 1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
• No prior therapy for pancreatic cancer, including chemotherapy, radiation therapy, definitive surgery or investigational therapy
• Members of all races and ethnic groups will be included
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count \>= 1.5 K/cu mm
• Platelets \>= 100 K/cu mm
• Hemoglobin \>= 9.0 g/dL

You may not qualify if:

• Subjects with locally advanced, unresectable primary tumors will not be eligible
• This includes any of the following:
• Abutment of the SMA \>= 180 degrees
• Occlusion of the SMV or PV with insufficient normal vein above and below with which to perform venous reconstruction
• Involvement of the hepatic artery with insufficient artery proximal and distal to perform reconstruction
• Any prior therapy (chemotherapy, radiation or surgery) for pancreatic adenocarcinoma other than biliary decompression
• Subjects who are receiving any other investigational agents
• Subjects with known metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABRAXANE or other agents used in the study
• Active infection requiring intravenous antibiotics at the time of registration
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of interstitial lung disease, idiopathic pulmonary fibrosis, silicosis, sarcoidosis or connective tissue disorders (including rheumatoid arthritis and systemic lupus erythematosus)
• Pregnant or breastfeeding women are excluded from this study
• Subjects known to be human immunodeficiency virus (HIV)-positive, including those on combination antiretroviral therapy, are ineligible because of the potential for pharmacokinetic interactions with chemotherapy; in addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy
• Subjects with plastic biliary stents will be excluded; metal biliary stents are allowed and will not be excluded

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Interventions

Fluorouracil; dehydroftorafur; Gemcitabine; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Radiotherapy; Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations

Limitations and Caveats

Study closed early due to lack of enrollment. Study was expected to enrolled 44 evaluable patients to achieve 83% power using the 2-sided binomial test at 10% significance. Study enrolled only 19 evaluable patients, meaning the study was underpowered at \< 62%. Study completed stage 1 of Simon's 2-stage minimax design and achieved the required goal of 8 R0 resections.

Results Point of Contact

• Title: Dr. Gina Vaccaro
• Organization: OHSUKCI

vaccarog@ohsu.edu

503-216-6300

Study Officials

• Gina Vaccaro

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2015
• First Posted: April 28, 2015
• Study Start: January 21, 2016
• Primary Completion: November 12, 2019
• Study Completion: December 12, 2022
• Last Updated: September 6, 2023
• Results First Posted: January 14, 2021

Record last verified: 2023-08

Locations

US (1)